Extended Classical Over-Barrier Model for Collisions of Highly Charged Ions with Conducting and Insulating Surfaces

We have extended the classical over-barrier model to simulate the neutralization dynamics of highly charged ions interacting under grazing incidence with conducting and insulating surfaces. Our calculations are based on simple model rates for resonant and Auger transitions. We include effects caused by the dielectric response of the target and, for insulators, localized surface charges. Characteristic deviations regarding the charge transfer processes from conducting and insulating targets to the ion are discussed. We find good agreement with previously published experimental data for the image energy gain of a variety of highly charged ions impinging on Au, Al, LiF and KI crystals.Comment: 32 pages http://pikp28.uni-muenster.de/~ducree

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media

Effect of transport-induced charge inhomogeneity on point-contact Andreev reflection spectra at ferromagnet-superconductor interfaces

We investigate the transport properties of a ferromagnet-superconductor interface within the framework of a modified three-dimensional Blonder-Tinkham-Klapwijk formalism. In particular, we propose that charge inhomogeneity forms via two unique transport mechanisms, namely, evanescent Andreev reflection and evanescent quasiparticle transmission. Furthermore, we take into account the influence of charge inhomogeneity on the interfacial barrier potential and calculate the conductance as a function of bias voltage. Point-contact Andreev reflection (PCAR) spectra often show dip structures, large zero-bias conductance enhancement, and additional zero-bias conductance peak. Our results indicate that transport-induced charge inhomogeneity could be a source of all these anomalous characteristics of the PCAR spectra.Comment: 9 pages, 6 figure

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Real-Life Anti-Tumour Necrosis Factor Experience in > 500 Paediatric United Kingdom Inflammatory Bowel Disease Patients.

OBJECTIVES: To measure the effectiveness, safety and use of anti-Tumour necrosis Factor (TNF) therapy in paediatric inflammatory bowel disease (PIBD) in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment (PGA) +/or the Paediatric Crohn's Disease Activity Index (PCDAI). RESULTS: 37 centres participated (23 of 25 specialist PIBD sites). 524 patients were included; 429 Crohn's disease (CD), 76 ulcerative colitis (UC), 19 IBD unclassified (IBDU). 87% (488/562) anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (IQR 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by PGA compared to 41% (88/217) by PCDAI; Kappa (Κ) 0.28 = only 'fair agreement' (p < 0.001).Where documented, 77% (53/69) of CD patients responded to induction; and 65% (46/71) entered remission. 2287 infusions and 301.96 years of patient follow-up (n = 385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Perianal abscess drainage was less common after anti-TNF initiation (CD): 26% (27/102) before, 7% (3/42) after (p = 0.01); however pre and post anti-TNF data collection was not over equal time periods. CONCLUSION: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools which need to be addressed to improve ongoing patient care

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

Next generation interactive tool as a backbone for universal access to electricity

Energy planning in rural areas and in developing countries most often relies on the outputs of specialized analytical tools, of which only a handful have been developed. Over the years these tools have been upgraded, and the newest among them take into consideration, to a greater or lesser extent, all key determinants of energy generation and distribution. This article focuses on a “pool” of web‐based geo‐referencing open‐source tools and highlights the extent to which each analytical tool reflects the particularities of the various determinants of energy generation and distribution. In doing so, the present work identifies aspects of the tools that need to be strengthened. Building on this information, the article further maps the suitability of each tool with regard to calculating (at a local level) the six Sustainable Development Goal indicators that are closely related to energy. This makes it possible to draw conclusions about monitoring needs in study‐areas. Bringing together these two sets of findings, the article concludes with a research agenda for analytical tool development in the area of energy planning, which spills over developmental agendas

Fluctuations in active membranes

Active contributions to fluctuations are a direct consequence of metabolic energy consumption in living cells. Such metabolic processes continuously create active forces, which deform the membrane to control motility, proliferation as well as homeostasis. Membrane fluctuations contain therefore valuable information on the nature of active forces, but classical analysis of membrane fluctuations has been primarily centered on purely thermal driving. This chapter provides an overview of relevant experimental and theoretical approaches to measure, analyze and model active membrane fluctuations. In the focus of the discussion remains the intrinsic problem that the sole fluctuation analysis may not be sufficient to separate active from thermal contributions, since the presence of activity may modify membrane mechanical properties themselves. By combining independent measurements of spontaneous fluctuations and mechanical response, it is possible to directly quantify time and energy-scales of the active contributions, allowing for a refinement of current theoretical descriptions of active membranes.Comment: 38 pages, 9 figures, book chapte

Proteomic Analysis of Polypeptides Captured from Blood during Extracorporeal Albumin Dialysis in Patients with Cholestasis and Resistant Pruritus

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis

Multi-Scale Sampling to Evaluate Assemblage Dynamics in an Oceanic Marine Reserve

To resolve the capacity of Marine Protected Areas (MPA) to enhance fish productivity it is first necessary to understand how environmental conditions affect the distribution and abundance of fishes independent of potential reserve effects. Baseline fish production was examined from 2002–2004 through ichthyoplankton sampling in a large (10,878 km2) Southern Californian oceanic marine reserve, the Cowcod Conservation Area (CCA) that was established in 2001, and the Southern California Bight as a whole (238,000 km2 CalCOFI sampling domain). The CCA assemblage changed through time as the importance of oceanic-pelagic species decreased between 2002 (La Niña) and 2003 (El Niño) and then increased in 2004 (El Niño), while oceanic species and rockfishes displayed the opposite pattern. By contrast, the CalCOFI assemblage was relatively stable through time. Depth, temperature, and zooplankton explained more of the variability in assemblage structure at the CalCOFI scale than they did at the CCA scale. CalCOFI sampling revealed that oceanic species impinged upon the CCA between 2002 and 2003 in association with warmer offshore waters, thus explaining the increased influence of these species in the CCA during the El Nino years. Multi-scale, spatially explicit sampling and analysis was necessary to interpret assemblage dynamics in the CCA and likely will be needed to evaluate other focal oceanic marine reserves throughout the world